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Polypoidal choroidal vasculopathy (PCV) occurs in the middle-aged and elderly population and is characterized by abnormal intrachoroidal vascular patterns such as branching choroidal vascular networks and polypoidal dilatation of vessel terminals, subretinal orange nodular lesions and hemorrhagic or plasma retinal pigment epithelial detachment (PED), which can cause retinal hemorrhage or vitreous hematopoiesis and is one of the major blinding fundus lesions.Intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs is currently the main method of PCV treatment, and has certain advantages in eliminating abnormal vascular networks and removing polypoidal lesions, reducing vascular exudation and promoting exudate absorption, and improving visual prognosis.However, frequent intravitreal drug injections increase the risk of infection and the treatment burden for patients.In addition, the high recurrence rate after treatment poses a significant challenge to clinical practice, so the search for new therapeutic agents that are durable and less costly is a focus of clinical research in PCV.The literature from abroad suggests that brolucizumab is a novel small-molecule anti-VEGF humanized monoclonal antibody with the advantages of high tissue penetration, high local drug concentration and bioavailability, small injectable dose, long-lasting efficacy and long injection interval, which brings new hope for the clinical treatment of PCV and improving the prognosis of affected eyes.Although the efficacy and safety of brolucizumab in the treatment of PCV have been well documented, the literature is mainly from Japan, India and Korea, and clinical practice data from China are still lacking.With the approval of the drug in several countries, it is believed that more PCV patients could benefit from this treatment in the near future.Ophthalmologists and researchers in China should closely follow the progress of brolucizumab in the treatment of PCV.
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Neovascularization is the hallmark of many fundus diseases, including diabetic retinopathy, retinal vein occlusion and neovascular age-related macular degeneration.More and more evidence suggests that vascular endothelial growth factor (VEGF) plays a critical role in neovascularization.Anti-VEGF drugs are the first-line treatment for neovascular fundus diseases and have achieved significant results.However, there are drawbacks such as short drug half-lives and the need for long-term administration to maintain effective concentrations, which increases the economic burden and medical risk for patients and reduces compliance.Therefore, finding a new method for intraocular drug delivery is of great clinical importance.Based on the principle that diabetes patients use insulin pumps to gradually release drugs, the ocular anti-VEGF drug delivery system can continuously release anti-VEGF drugs over a period of time, significantly reducing the injection frequency and improving patient compliance.At present, the research on ocular anti-VEGF drug delivery systems is still immature, and various systems are in different stages of clinical trials.According to different design principles, they can be divided into three categories with their characteristics, micropump (extraocular storage delivery systems), biodegradable implants, and non-biodegradable implants.This article summarized and analyzed the controlled ocular anti-VEGF drug release delivery systems currently in clinical trials.
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Objective:To investigate the effect of small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) in mouse model of retinal light injury and the possible mechanism.Methods:Human umbilical cord derived MSCs were identified by flow cytometry.Supernatants of passage 3-5 MSCs were collected.sEVs were harvested by ultracentrifugation and were identified by transmission electron microscopy.Sixty-five healthy female SPF-grade BALB/c mice aged 8-10 weeks were randomly divided into normal group (17 mice), phosphate buffered saline (PBS) group (24 mice) and sEVs group (24 mice). Mice in PBS and sEVs groups were intravitreally injected with 2 μl of PBS and sEVs, respectively, and were exposed to 930 lx blue light for 6 hours.No intervention was administered to the normal group.Three days after lighting, mice retinal structure was observed by hematoxylin-eosin staining.Apoptotic retinal cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Retinal function was tested by electroretinogram.Differentially expressed mRNAs between PBS group and sEVs group were assayed by mRNA transcriptome sequencing and were analyzed through KEGG cluster analysis.The differential mRNAs were verified via real-time quantitative PCR.The study protocol was approved by the Animal Ethics Committee of Tianjin Medical University Eye Hospital (No.TJYY20201221035).Results:MSCs were positive for CD90 and CD105, negative for CD34 and CD45.The extracted MSC-sEVs showed a bilayer membrane vesicle with a diameter of 80-140 nm.Hematoxylin-eosin staining showed the arrangement of photoreceptor nuclei was disordered in outer nuclear layer in PBS group.The disorder of photoreceptor nuclei arrangement of sEVs group was slighter than that of PBS group.The apoptotic cell number of sEVs group was (14.60±4.04)/visual field, which was lower than (24.00±8.52)/visual field of PBS group, with a statistically significant difference ( t=2.37, P<0.05). The a-wave amplitude of sEVs group was (64.38±16.70)μV, which was higher than (16.78±6.37) μV of PBS group, showing a statistically significant difference ( P<0.05). The b-wave amplitudes of PBS and sEVs groups were (132.40±39.41) μV and (154.86±34.08) μV, respectively, which were lower than (338.38±27.41) μV of normal group, and the differences were statistically significant (both at P<0.05). A total of 110 differentially expressed mRNAs were detected.There were 109 downregulated mRNAs in sEVs group.Differentially expressed mRNAs were mainly inflammation- and immune-related pathways.PCR showed that the expression level of C-C motif chemokine ligand 2, C-C motif chemokine receptor 2, leukotriene B4, leukocyte Ig-like receptor A6 and interleukin-1β in sEVs group were significantly decreased in comparison with PBS group (all at P<0.05). Conclusions:MSC-sEVs can ameliorate blue light-induced retinal structural and functional damage.The protective effect may be achieved through inhibiting inflammatory response.
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Diabetic macular edema (DME) is the most threatening complication of diabetic retinopathy that affects visual function, which is characterized by intractability and recurrent attacks. Currently, the clinical routine treatments for DME mainly include intravitreal injection, grid laser photocoagulation in the macular area, subthreshold micropulse laser, periocular corticosteroid injection, and vitrectomy. Although conventional treatments are effective for some patients, persistent, refractory, and recurrent DME remains a clinical challenge that needs to be urgently addressed. In recent years, clinical studies have found that certain combination therapies are superior to monotherapy, which can not only restore the anatomical structure of the macular area and effectively reduce macular edema but also improve visual function to some extent while reducing the number of treatments and the overall cost. This makes up for the shortcomings of single treatment modalities and is highly anticipated in the clinical setting. However, the application of combination therapy in clinical practice is relatively short, and its safety and long-term effectiveness need further exploration. Currently, new drugs, new formulations, and new therapeutic targets are still under research and development to address different mechanisms of DME occurrence and development, such as anti-vascular endothelial growth factor agents designed to anchor repetitive sequence proteins with stronger inhibition of vascular leakage, multiple growth factor inhibitors, anti-inflammatory agents, and stem cell therapy. With the continuous improvement of the combination application of existing drugs and treatments and the development of new drugs and treatment technologies, personalized treatment for DME will become possible.
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Objective:To compare and analyze the application of anti-vascular endothelial growth factor (VEGF) drugs for intravitreal injection in the real world before and after the establishment of one-stop intravitreal injection center, as well as the advantages and disadvantages of different management modes.Methods:A retrospective clinical study. A total of 4 015 patients (4 659 eyes) who received anti-VEGF drugs for ocular fundus diseases at the Tianjin Medical University Eye Hospital from July, 2018 to June, 2022 were included in the study. There were 2 146 males and 1 869 females. The ocular fundus diseases in this study were as follows: 1 090 eyes of 968 patients with wet age-related macular degeneration (wAMD); 855 eyes of 654 patients with diabetic macular edema (DME); 1 158 eyes of 980 patients with diabetic retinopathy (DR); 930 eyes of 916 patients with macular edema secondary to retinal vein occlusion (RVO-ME). A total of 294 eyes of 275 patients with choroidal neovascularization secondary to pathological myopia (PM-CNV); 332 eyes of 222 patients with other fundus diseases. A total of 13 796 anti-VEGF needles were injected. A total of 1 252 patients (1 403 eyes) from July 2018 to June 2020 were regarded as the control group. From July 2020 to June 2022, 2 763 patients (3 256 eyes) who received anti-VEGF treatment in the intravitreal injection center were regarded as the observation group. The total number of intravitreal injection needles, the distribution of anti-VEGF therapy in each disease according to disease classification, the proportion of patients who chose the 3+ on-demand treatment (PRN) regimen and the distribution of clinical application of different anti-VEGF drugs were compared between the control group and the observation group. The waiting time and medical experience of patients were investigated by questionnaire. χ2 test was used to compare the count data between the two groups, and t test was used to compare the measurement data. Results:Among the 13 796 anti-VEGF injections in 4 659 eyes, the total number of anti-VEGF drugs used in the control and observation groups were 4 762 and 9 034, respectively, with an average of (3.39±3.78) and (2.78±2.27) injections per eye ( t=6.900, P<0.001), respectively. In the control and observation groups, a total of 1 728 and 2 705 injections of anti-VEGF drugs were used for wAMD with an average of (5.14±4.56) and (3.59±2.45) injections per eye, respectively; a total of 982 and 2 038 injections of anti-VEGF drugs were used for DME with an average of (4.36±4.91) and (3.24±2.77) needles per eye, respectively. Additionally, a total of 942 and 2 179 injections of anti-VEGF drugs were injected for RVO-ME with an average of (3.98±3.71) and (3.14±2.15) injections per eye, respectively; a total of 291 and 615 injections of anti-VEGF drugs were injected for PM-CNV with an average of (3.31±2.63) and (2.99±1.69) injections per eye, respectively. A total of 683 and 1 029 injections of anti-VEGF drugs were injected for DR with an average of (1.60±1.26) and (1.41±1.05) injections per eye, respectively. The clinical application and implementation of "3+PRN" treatment were as follows: 223 (66.4%, 223/336) and 431 eyes (57.2%, 431/754) in the wAMD ( χ2=8.210, P=0.004), 75 (33.3%, 75/225) and 236 (37.5%, 236/630) eyes in the DME ( χ2=1.220, P>0.05), and 97 (40.9%, 97/237) and 355 eyes (51.2%, 355/693) in the RVO-ME ( χ2=7.498, P=0.006), 39 (44.3%, 39/88) and 111 eyes (53.9%, 111/206) in the PM-CNV ( χ2=2.258, P>0.05), respectively. In addition, the results of the questionnaire survey showed that there were significant differences between the control and observation groups regarding the time of appointment waiting for surgery ( t=1.340), time from admission to entering the operating room on the day of injection ( t=2.780), time from completing preoperative treatment preparation to waiting for entering the operating room ( t=8.390), and time from admission to discharge ( t=6.060) ( P<0.05). Conclusions:The establishment of a one-stop intravitreal injection mode greatly improved work efficiency and increased the number of injections. At the same time, the compliance, waiting time, and overall medical experience of patients significantly improved under centralized management.
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Objective:To analyze the risk factors of postoperative vitreous hemorrhage (PVH) after pars plana vitrectomy (PPV) for vitreous hemorrhage (VH) secondary to retinal vein occlusion (RVO).Methods:A retrospective case-control study. A total of 195 RVO patients (195 eyes) with VH were first treated with PPV from November 2015 to December 2021 were included in this study. There were 102 males (102 eyes) and 93 females (93 eyes), with an age of (62.93±9.78) years. The patients were divided into PVH group (17 patients, 8.72%) and non-PVH group (178 patients, 91.28%) according to the occurrence of PVH. The time of occurrence of PVH was (140.33±130.85) days after PPV. All eyes were performed 23G or 25G systematic PPV by the same doctor. During the operation, different types of intraocular tamponade and intravitreal injection of anti-vascular endothelial growth factor or triamcinolone acetonide after operation were selected according to the severity of retinopathy. The follow-up time was (9.45±6.68) months. The baseline systemic parameters, ocular parameters and intraoperative parameters affecting the occurrence of PVH were analyzed. Baseline systemic parameters included sex, age, diabetes mellitus and hypertension; ocular parameters included RVO type, lens status, VH course, preoperative best corrected visual acuity and intraocular pressure; intraoperative parameters included cataract phacoemulsification, removal of internal limiting membrane, type of intraocular tamponade, type of intravitreal injection drug at the end of operation, etc. Kaplan-Meier survival analysis, and Cox univariate and multivariate regression analysis were performed to analyze the risk factors of PVH after PPV in RVO with VH patients.Results:In PVH group, the number of patients with diabetes was more than that in the non-PVH group, and the course of diabetes was longer, and differences were statistically significant. There were significant differences in RVO type, lens status and type of intraocular tamponade. Univariate Cox regression analysis showed that the combination with diabetes [odds ratio ( OR)=2.724, 95% confidence interval ( CI) 1.006-7.374, P=0.049], duration of diabetes ( OR=1.071, 95% CI 1.013-1.134, P=0.016), central retinal vein occlusion ( OR=4.387, 95% CI 1.421-13.546, P=0.010), intraocular lens ( OR=3.493, 95% CI 1.229-9.925, P=0.019), and intraocular gas tamponade ( OR=3.640, 95% CI 1.365-9.702, P=0.010) were associated with PVH. Multivariate Cox regression analysis showed that intraocular gas tamponade was independent risk factor for PVH. Conclusion:Intraocular gas tamponade can increase the risk of PVH after PPV in patients with VH secondary to RVO.
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Endogenous pigment epithelium derived factor (PEDF) shows great potential as a drug target for the treatment of diabetes retinopathy (DR) due to its anti-angiogenesis, anti-inflammatory, neuroprotective and neurotrophic effects. PEDF plays a biological role by combining with receptor proteins on cell membrane surface and regulating a variety of signaling pathways. Low density lipoprotein receptor related protein 6 plays a role in inhibiting oxidative stress reaction, inflammatory reaction, and neovascularization of DR. Adipose triglyceride lipase, laminin receptor, plexin domain containing 1 (PLXDC) 1, PLXDC2 and F 1-adenosine triphosphate synthase have the effect of promoting endothelial cell apoptosis, among which PLXDC1 also has neuroprotective effect. By clarifying the receptor that PEDF acts on, exploring the affinity between the receptor and PEDF, the difference in the expression level of each receptor in the process of disease, and the specific function that PEDF plays after binding with specific receptors, we can develop fusion protein drugs for the active domain of high affinity of receptors, have a clearer understanding of the pathogenesis of DR, and take PEDF or PEDF receptor as the target to consolidate the theoretical basis for the development of new therapeutic drugs and strategies for DR.
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Intravitreal drug injection is a treatment for common chronic fundus diseases such as age-related macular degeneration and diabetic retinopathy. The "14th Five-Year" National Eye Health Plan (2021-2025) recommends focusing on fundus diseases and improve the management mode of patients with chronic eye diseases. Therefore, it is imperative to explore how to further optimize the service process of intravitreal injection under the premise of guaranteeing patients' medical safety, to promote medical service efficiency and standardized management level and improve the medical experience of patients. Based on the quality control standard of vitreous cavity injection for retinopathy in China, Chinese fundus disease and related field experts developed the present expert consensus on the establishment of a one-stop intravitreal injection model and the management of its organization after a serious, comprehensive, and complete discussion, focusing on a standardized operation process, quality control, and safety management, providing more references for establishing a suitable intravitreal injection management model for ophthalmology and promoting the development of diagnostic and treatment models for fundus disease in China.
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Diabetic retinopathy (DR) is one of the serious complications of diabetes, and its complex pathogenesis has not been completely clarified yet.Metabolic changes are closely related to phenotypes and metabolomics analysis can indicate the biochemical status of cells, tissues or organs.With the renewal of metabolomics technology and the improvement of detection sensitivity, more differential metabolites have been detected.Therefore, metabolomics has gradually become a powerful tool to explore the pathogenesis of DR and the therapeutic potential of drugs for DR.Metabolomics study in DR is still in its infancy, which mainly takes vitreous humor, aqueous humor and plasma as samples with the pentose phosphate pathway, arginine and proline pathway and ascorbic acidic pathway as main research pathways.Further research is necessary to explore the pathogenesis, diagnosis and treatment of DR, and to determine its longitudinal association with the disease.Metabolomics studies related to the animal model of DR and the vitreous humor, aqueous humor and plasma of DR patients were reviewed in this article.
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Size of the macular hole (MH) is an important factor affecting the treatment of MH.MH with a diameter >400 mm was defined as large MH.Pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) peeling or intravitreal gas tamponade, which can effectively relieve the traction of vitreoretinal interface, is the standard surgical technique for idiopathic full-thickness macular hole (FTMH), but its efficacy on refractory large FTMH is very limited.In order to obtain ideal anatomical healing and functional recovery of large FTMH, new surgical strategies, such as reversal of retinal internal limiting membrane (ILM), expanded removal of ILM, transplantation of different tissue valves, application of mesenchymal stem cells and so on, have been the focus of researchers in the field of fundus diseases.More targeted and personalized treatment is the development trend of treatment for large FTMH.The progress of ILM flipping surgery, expansion of ILM removal, transplantation of different tissue valves, biomaterials and other auxiliary techniques in the treatment of large diameter FTMH were reviewed in this article.
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Objective:To quantitatively analyze the protein expression changes of the optic nerve in an SD rat model of non-arteritic anterior ischemic optic neuropathy (NAION), and to make bioinformatics analysis of the differential proteins.Methods:Ten 8-week-old SPF male SD rats with a body mass of 200-250 g were selected.The NAION model was established using the method of rose bengal and laser photodynamics.Four from the 8 rats with successful model were selected as the NAION model group.Another 4 body weight- and age-matched healthy SD rats without eye diseases were taken as the normal control group.The optic nerve was dissected on the 7th day after modeling.The samples were prepared by the enzyme digestion method, and the proteins were identified and quantitatively detected by isobaric tag for relative and absolute quantification labeling combined with liquid chromatography-tandem mass spectrometry.The proteins with expression fold greater than 1.5 times and significant differences between the two groups ( P<0.05) were defined as differentially expressed proteins and analyzed by bioinformatics.The use and care of animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by the State Science and Technology Commission of China.The study protocol was approved by an Animal Ethical and Welfare Committee of Tianjin Medical University Eye Hospital (No.TJYY2021041029). Results:Three days after modeling, the optic disc of rats was swollen and fluorescein leakage in the optic disc was detected in fluorescein fundus angiography images in the NAION model group, which indicated the model was established successfully.A total of 1 291 quantifiable proteins including 80 differentially expressed proteins were identified.Compared with the normal control group, there were 5 up-regulated proteins and 75 down-regulated proteins.The expression levels of collagen alpha-1(V) chain (Col5A1), cAMP-dependent protein kinase catalytic subunit beta (Prkacb) and disks large homolog 1(Dlg1) were increased, and the expression levels of neurofilament medium polypeptide (Nefm), microtubule-associated protein 1B (Map1b), Ras-related protein Ral-A (Rala), serine/threonine-protein kinase N2 (Pkn2) and platelet-activating factor acetylhydrolase IB subunit beta (Pafah1b1) were decreased.Differentially expressed proteins were mainly involved in the biological processes, including regulation of the cytoskeleton, cellular response to hypoxia, axon production and extension, regulation of synapse, regulation of neuron apoptosis and axo-dendritic transport, etc.KEGG pathway enrichment analysis showed that differentially expressed proteins were mainly involved in metabolic pathways, synaptic vesicle circulation and platelet activation.Conclusions:The expression of proteins related to signal pathways such as nerve growth, energy metabolism, axo-dendritic transport and apoptosis is involved in the apoptosis of neurons in NAION.
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Objective:To explore the clinical application of lateral thoracic artery perforator flap in repairing local defect after breast conserving surgery.Methods:The clinical data of 48 breast cancer patients planned to finish breast conserving surgery were retrospectively analyzed. The patients were divided into plastic breast-conserving group and routine breast conserving group. In the plastic breast-conserving group, 24 patients local defect repaired with the lateral thoracic artery perforator flap. In the routine breast conserving group, 24 patients local defect repaired with the fascial flap around the cutting edge. The operation related indexes and cosmetic effect from two groups were compared.Results:Both groups of patients successfully completed breast conserving surgery. The plastic breast-conserving group patients had significantly increased in operation time, operative blood loss, incision length and drainage tube indwelling time compared with the routine breast conserving group; the differences were statistically significant ( t=6.99, 9.37, 21.74, 8.80, P<0.05). The rate of secondary surgery enlarged was lower than fhat in the routine breast conserving group, and the difference was statistically significant (χ 2=4.76, P<0.05). There were 3 cases in the plastic breast conserving group and 1 case in the conventional breast conserving group. The skin at the edge of the flap was ischemic necrosis in the 4 cases, which healed after dressing change and drainage, and there was no significant difference ( P>0.05). The evaluation of postoperative cosmetic effect showed that the excellent and good rate of the observation group was 91.7%, compared with the routine breast conserving group (58.3%); the difference was statistically significant (χ 2=7.11, P<0.05). All patients were followed up for average 24 months, and local recurrence and distant metastasis were not observed. Conclusions:The lateral thoracic artery perforator flap for filling local defects in the lateral quadrant or central region of breast cancer is feasible, easy to operate, hides incision scar, better cosmetic effect and worthy of clinical promotion.
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Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, and it is the main cause of vision loss in diabetic patients. Angiopoietin (Ang), a superfamily of secreted proteins, is a vascular growth factor that regulates the stability of vascular environment, participates in angiogenesis and repair, and lipid metabolism. It plays an important role in the development of DR and has become a new target for the treatment of diabetic retinopathy. With the in-depth study of Ang and the research and development of various drugs for Ang, it is expected to bring new ideas and strategies for the treatment of DR in the future.
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Objective:To observe the expression of miRNA in retinal tissue of mice with oxygen-induced retinopathy (OIR), and screen miRNAs related to p21 and retinal neovascularization (RNV) formation.Methods:A experimental study. Forty healthy 7-day-old C57BL/6J mice were randomly divided into normal group and OIR group, with 20 mice in each group. The oxygen induced RNV model was constructed in the OIR group, and no treatment was performed in the normal group. At the age of 17 days, the mice were killed and the RNV of mice was observed by retinal fluorescence; the nuclei of vascular endothelium that broke through the inner limiting membrane of retina were counted under light microscope. The retinal tissues were taken for miRNA chip analysis to detect the differentially expressed miRNAs between the normal group and the OIR group. The resulting differential miRNA target genes were subjected to enrichment analysis based on gene annotation (GO) and Kyoto Encyclopedia of genes and genomes (KEGG); miRNAs and pathways that may be related to p21 were screened through Targetscan, MiRanda and MicroT-CDs database alignment. Independent sample t-test was used for pairwise comparison between groups. Results:Compared with the normal group, the area of nonperfusion area, RNV and the number of vascular endothelial nuclei that broke through the inner limiting membrane of the retina in the OIR group increased significantly, differences were statistically significant ( t=18.800, 9.025; P<0.05). Compared with the normal group, there were 54 miRNAs that were statistically differentially expressed in the OIR group, of which 47 were up-regulated and 7 were down-regulated. A total of 13 miRNAs related to p21 were screened from the alignment results of the three databases with the obtained differential miRNAs. According to the difference multiples, they were miR-7218-5p, miR-322-5p, miR-224-5p, miR-335-5p, miR-329-3p, miR-362-3p, miR-532-5p, miR-20b-5p, miR-20a-5p, miR-195a-5p, miR-423-5p, miR-497a-5p, and miR-129-5p. Differential miRNA target gene enrichment analysis yielded 1 112 go entries and 50 KEGG pathways, of which 50 go entries and 13 KEGG pathways were related to p21. Conclusion:13 miRNAs related to p21 were screened out in the OIR model.
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Objective:To observe the expression of miRNA in retinal tissue of mice with oxygen-induced retinopathy (OIR), and screen miRNAs related to p21 and retinal neovascularization (RNV) formation.Methods:A experimental study. Forty healthy 7-day-old C57BL/6J mice were randomly divided into normal group and OIR group, with 20 mice in each group. The oxygen induced RNV model was constructed in the OIR group, and no treatment was performed in the normal group. At the age of 17 days, the mice were killed and the RNV of mice was observed by retinal fluorescence; the nuclei of vascular endothelium that broke through the inner limiting membrane of retina were counted under light microscope. The retinal tissues were taken for miRNA chip analysis to detect the differentially expressed miRNAs between the normal group and the OIR group. The resulting differential miRNA target genes were subjected to enrichment analysis based on gene annotation (GO) and Kyoto Encyclopedia of genes and genomes (KEGG); miRNAs and pathways that may be related to p21 were screened through Targetscan, MiRanda and MicroT-CDs database alignment. Independent sample t-test was used for pairwise comparison between groups. Results:Compared with the normal group, the area of nonperfusion area, RNV and the number of vascular endothelial nuclei that broke through the inner limiting membrane of the retina in the OIR group increased significantly, differences were statistically significant ( t=18.800, 9.025; P<0.05). Compared with the normal group, there were 54 miRNAs that were statistically differentially expressed in the OIR group, of which 47 were up-regulated and 7 were down-regulated. A total of 13 miRNAs related to p21 were screened from the alignment results of the three databases with the obtained differential miRNAs. According to the difference multiples, they were miR-7218-5p, miR-322-5p, miR-224-5p, miR-335-5p, miR-329-3p, miR-362-3p, miR-532-5p, miR-20b-5p, miR-20a-5p, miR-195a-5p, miR-423-5p, miR-497a-5p, and miR-129-5p. Differential miRNA target gene enrichment analysis yielded 1 112 go entries and 50 KEGG pathways, of which 50 go entries and 13 KEGG pathways were related to p21. Conclusion:13 miRNAs related to p21 were screened out in the OIR model.
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Objective:To observe clinical phenotypes and analyze the pathogenic genes of Leber congenital amaurosis (LCA).Methods:A retrospective clinical study. From 2019 to 2020, 2 patients diagnosed with LCA by genetic testing in Tianjin Medical University Eye Hospital and their 6 unaffected family members were enrolled in the study. Two patients were from 2 unrelated families, both were probands. The patient's medical history was inquired in detail, slit lamp microscopy, ultra-widefield fundus photography, autofluorescence, and flash visual evoked potential (F-VEP) were performed. Peripheral vein blood (3-5 ml) was collected and genomic DNA was extracted from all study subjects. A total of 381 pathogetic genes associated with inherited retinal diseases, were selected by targeted exome sequencing capture strategy. Sanger sequencing was used to verify suspected pathogenic mutations. Candidate pathogenic mutations were identified after bioinformatics analysis. Sanger sequencing, real-time quantitative polymerase chain reaction and family co-identification were used to confirm the final mutations.Results:Two patients were male, aged 3 and 27 years. One case had vision loss in both eyes, accompanied by nystagmus and acupressure eye sign since childhood. The clinical hallmark of the proband (F1-Ⅱ-3) in F1 includes clearly boundary of optic disc, normal retinal blood vessels and macular fovea. The implied period of the maximum forward wave in both eyes of F-VEP was roughly normal, and its amplitude decreased significantly. The phenotype of the proband (F2-Ⅱ-1) in F2 includes optic nerve head pallor, bone-spicule intraretinal pigmentation, "gold-foil maculopathy" , retina patchy hypo-autofluorescence in both eyes. There was no abnormal phenotype in the eyes of the family members. According to the genetic diagnosis, the proband (F1-Ⅱ-3) carried the GUCY2D gene c.835G>A (p.D279N) (M1) and exon 9-19 deletion (M2) compound heterozygous mutations, in which M1 was derived from healthy mother and M2 was derived from healthy father. The proband (F2-Ⅱ-1) carried CRB1 gene c.1576C>T(R526X) (M3) and c.1522T>C (C508R) (M4) compound heterozygous mutations, in which M3 from the healthy father, M4 from the healthy mother. M2 and M4 were novel mutations. Conclusion:GUCY2D gene mutations lead to LCA1 type in the F1 family, CRB1 gene mutations lead to LCA8 type in the F2 family; there are significant different phenotypes caused by different pathogenic genes.
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Endothelial progenitor cells (EPCs) are progenitor cells possessing vasculogenic potential.The main function of EPCs is to play a role by paracrine angiogenic factors and neuroprotective factors.EPCs also have the ability to differentiate into endothelial cells and integrate themselves into newly formed capillaries.Therefore, EPCs play an important role in vascular repair and neuroprotection.The research on surface markers and functions of EPCs is the basis of EPCs research.A series of clinical trials, animal and cell experiments show that EPCs transplantation and joint transplantation of EPCs and other cells can promote vascular repair and improve retinal function with good safety.EPCs are expected to be an effective treatment for diabetic retinopathy (DR). DR is now defined as a refractory eye disease with retinal neurovascular unit (NVU) injury associated with systemic metabolism anbormality.Change in EPCs count and damage of EPCs function are involved in the occurrence and development of DR.Ophthalmologists should pay attention to the early managing approach of EPCs.Current treatment strategies include transplantation of EPCs, joint transplantation of EPCs with other cells, and regulation of endogenous EPCs.The unique biological characteristics of EPCs provide many possibilities in repairing retinal NVU injury and DR prevention and treatment.This article introduces the latest research progress of EPCs for DR from five aspects including the origin of EPCs, physiological and pathological state, function, treatment strategy and clinical application.At the same time, the existing problems and technical bottlenecks will also be discussed.
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Diabetic retinopathy (DR) is a common neurovascular complication of diabetes patients, which seriously threatens the vision health of working-age people and brings a heavy social and economic burden to our society.Most patients with DR have progressed to the stage of proliferative diabetic retinopathy and need to receive intravitreal injection of drugs or surgery but resulting in poor recovery of vision.Therefore, exploring new biomarkers is of great significance for the diagnosis and treatment of early DR.High-throughput proteomics research can examine smaller volumes of biological fluid specimen such as aqueous humor, vitreous humor, tears, and serum, finding differential proteins involved in inflammatory processes in the retina, providing references for the early diagnosis and treatment of DR.Proteomics techniques used for the screening and identification of inflammatory biomarkers in DR in recent years and existing problems were reviewed in this article.
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Diabetic retinopathy (DR) is a kind of common vascular complications in diabetes and one of the leading causes of irreversible blindness.It is characterized by leaky retinal vasculature, neovascularization and fiber membrane proliferation.Although there are various DR treatments, most of them aim at middle and late stage of the disease and have limited efficacy.Therefore, early diagnosis and precise treatment of DR are important.In recent years, the research of biomarkers related to DR has developed rapidly, which plays an important role in the risk assessment and early intervention of the disease.Nowadays, classic biomarkers such as HbA1c have been widely used in clinical practice.With the further study on DR, inflammatory biomarkers and angiogenesis-related biomarkers have been found to be closely related to the occurrence and development of the disease.At the same time, with the progress of modern technology, advanced equipment have built a broad platform for the exploration of DR biomarkers.Omics biomarkers, imaging biomarkers and artificial intelligence have become the focus of research and made important contributions to the early treatment of DR.This article summarized the key progress related to the DR biomarkers research to provide new clinical strategies in the efficient prevention, control and treatment of DR.
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Diabetic retinopathy (DR) is one of the complications of diabetic mellitus and a major cause of blindness worldwide.Early detection and treatment for DR could reduce the risk of blindness.With the development of high-throughput omics, proteomics and metabolomics have shown great advantages in early diagnosis, exploration of pathogenesis, and discovery of new therapeutic targets in DR.Although traditional biomarkers such as duration of diabetes and HbA1c are good predictors for the progression of DR, there is still a lack of independent predictors that can reflect the pathogenesis of DR.Advances in artificial intelligence and machine learning have facilitated the exploration of novel biomarkers for DR, making the novel biomarkers more noninvasive, robust and sensitive.In clinical practice, the analysis of proteins and metabolites in patients with varied prognosis may help clinicians understand the heterogeneity of patients to develop precision medicine in DR.This review summarized the progress in the technology and strategy of proteomics and metabolomics in biomarker discovery, pathogenesis, and precision medicine of DR to promote clinical and translational research in this field.